Coordinate changes in brain energy metabolism and protein synthesis are investigated using two models of altered brain metabolism -- amphetamine hyperthermia in mice, and transient ischemia in gerbils. Protein synthesis status is determined using and in vitro amino acid incorporation method which provides information analoguns to polyribosome profiles. Glycogen, glucose, phosphocreatine, adenine and guanine nucleotides and other metabolites are measured enzymatically. Previous studies in this laboratory have demonstrated that the inhibition of protein synthesis by amphetamine is a consequence of drug-induced hyperthermia, inhibition occurring abruptly between 40 and 41 C. Protein synthesis is affected in liver and kidney as well as brain, and the same effect is produced directly by warming the animals at 42 C. Brain glycogenolysis following amphetamine administration is more pronounced in hyperthermic animals, but does not correlate well with temperatures of individual mice. Other measures of energy status are not significantly affected. The reduction in brain protein synthesis is thus dissociated from effects on known components of energy metabolism. During transient ischemia in gerbils, brain metabolism is drastically altered, ATP, PCr and GTP being totally depleted. Within minutes of reperfusion, most measures of energy status have returned to control levels, while brain protein synthesis remians depressed for several hours. Of the several metabolites measured, we have found that only glycogen shows a delayed recovery comparable to that observed for protein synthesis. While a link between protein and glycogen metabolism remains to be established, this model holds considerable promise as an experimental system in which to investigate metabolic regulation of brain protein synthesis.